Cyclophosphamide, Doxorubicin, Vincristine, Prednisone plus Rituximab (CHOP-R) andCyclophosphamide, Pixantrone, Vincristine, Prednisone plus Rituximab (CPOP-R) inPatients with Diffuse Large-B-cell Lymphoma: A Phase II, Randomized,Multicenter, Comparative Trial

• Conditions: Diffuse large B-cell lymphoma.; MedDRA version: 13.1Level: PTClassification code 10012818Term: Diffuse large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2005-001100-40-DE
• Lead Sponsor: Cell Therapeutics Europe S.r.l.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-11-24
• Last Update Posted: 21 January 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 280

Inclusion Criteria

1. Previously untreated and histologically confirmed diffuse large B-cell lymphoma
according to REAL/WHO classification. The histological specimen, i.e. lymph node
biopsy slides or tissue blocks, used to determine eligibility must be available for
review.
2. Stage II, III or IV disease
3. CD20+
4. Age = 18 years
5. ECOG performance status of = 2
6. At least one objectively bidimensionally measurable lesion as demonstrated by CT,
spiral CT, or MRI that can be followed for response as target lesion. Patients with the
following sites of disease are NOT eligible:
• Patients with only skin lesions or only palpable lymph nodes.
• Patients with spleen or bone marrow as only site of disease.
7. Life expectancy = 3 months according to investigator’s opinion.
8. Serum bilirubin = 1.5 x the institution’s upper limit normal (ULN) and creatinine
=2.0 ULN and AST or ALT =2.0 x the institution’s ULN. If hepatic involvement by
lymphoma is present, AST or ALT may be =5.0 x the institution’s ULN.
9. LVEF = 50% determined by MUGA scan.
10. Ability to comply with the visit schedule and assessments required by the protocol.
11. Signed approved informed consent, with understanding of study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Any prior chemotherapy (except intrathecal chemotherapy at diagnosis and
pretreatment corticosteroid therapy) or radiotherapy. Patients may receive
corticosteroid pretreatment therapy for up to 7 days after randomization, if judged
appropriate by the investigator, to reduce tumor burden.
2. Histological diagnosis of T-cell lymphoma or any B-cell lymphoma other than diffuse
large B-cell.
3. History of indolent lymphoma
4. Active CNS involvement based on clinical evaluation (if the patient requires a
diagnostic lumbar puncture due to high risk criteria, i.e., sinus involvement, high
LDH, high IPI, or bone marrow involvement, intrathecal chemotherapy may be
administered according to institutional standards. This can include: methotrexate,
cytarabine and corticosteroids).
5. HIV-related lymphoma.
6. Major thoracic and/or abdominal surgery within the 4 weeks before randomization
from which the patient has not fully recovered except for diagnosis of NHL. Patients
who have had minor surgery may be enrolled after a =1 week recovery period except
for diagnosis of NHL.
7. Clinically significant cardiovascular abnormalities (equal to NYHA grade III - IV),
myocardial infarction within the prior 6 months, severe arrhythmia or uncontrolled
hypertension, history of CHF.
8. Serious (NCI CTCAE grade 3-4) intercurrent infection at randomization or deep
seated or systemic mycotic infections.
9. Clinical symptoms suggesting unresolved HIV, HBV or HCV infection. Patients with
seropositivity presumed to be due to prior vaccination against Hepatitis B virus or
resolved infection will not be excluded.
10. Active or history of another malignancy except cured basal cell carcinoma of skin or carcinoma in situ of uterine cervix. Patients who have been in remission from another previous malignancy for >5 years will be considered eligible.
11. Known hypersensitivity to the excipients or the study drugs that the patient will
receive.
12. Any contraindications to the study drugs as described in the Summary of Product
Characteristics or package inserts. These include but are not limited to urinary tract
disturbances (e.g. dysuria, any difficulty urinating) and increased bleeding affinity.
13. Neurological contraindication to vincristine (e.g. peripheral neuropathy).
14. Any condition which, in the judgment of the Investigator, would place the subject at undue risk, interfere with the results of the study, or make the subject otherwise
unsuitable.
15. General status that, in the opinion of the Investigator does not permit the
administration of eight courses of CHOP-R/CPOP-R.
16. Treatment with any other investigational study drug within 30 days before
randomization. Patient must have recovered from all side effects of other
investigational therapy.
17. Potentially fertile men and women and their sexual partners not willing to use
adequate contraception as defined by the Investigator during the study and for 6
months after the last day of study drug administration.
18. Any circumstance at the time of study entry that would preclude completion of the
study or the required follow-up.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to compare the response rate of the CPOP-R regimen with the standard CHOP-R regimen and to show that the response rate for CPOP-R is not inferior to that of CHOP-R.;Secondary Objective: Secondary objectives are to compare the Overall Survival, Progression-Free Survival, safety and tolerability of the two treatments, including cardiac function. Other comparisons will include: Duration of Response, Overall Objective Response rate, and Time to Treatment Failure.;Primary end point(s): The primary efficacy endpoint is complete objective response (CR) and unconfirmed<br>complete response (CRu) rate.